Equine infectious anemia (EIA) is a naturally occurring retroviral disease of Equidae characterized by a relapsing clinical course of viremia, fever, anemia, hepatitis, and glomerulitis. The virus replicates in macrophages throughout the body. Sequential emergency of one to several antigenic variants of the virus induces clinical relapses, then the disease usually progresses to an asymptomatic carrier state with viral persistence in infected cells. EIA is an important model for retroviral pathogenesis studies since the immune system is hypothesized to limit the clinical course, to select the emergence of viral antigenic variants, to contribute to the establishment of the asymptomatic (carrier) state, and to cause the pathologic lesions. We propose to test this hypothesis by comparing critical events during the course of infection in foals with naturally occurring combined immunodeficiency disease (CID), and in age matched normal foals. Since CID foals lack functional T and B cells but have normal macrophage numbers and function, this experimental system is uniquely suited for describing the role of the immune response in retroviral disease. This work will be accomplished by pursuing the following specific aims. 1. To determine whether viremia is controlled in CID foals infected with equine infectious anemia virus (EIAV). 2. To determine whether EIAV antigenic variants are expressed in CID foals infected with EIAV. 3. To determine whether tissue lesions occur in CID foals infected with EIAV.